Depressive illness is now widely recognized as a major cause of morbidity and mortality in old age. Although it represents a significant public health concern by virtue of its high cost in human suffering, disability, and potential for suicide, it has not been studied extensively, and specific criteria for optimal treatment are lacking. Depression in the elderly is also associated with poor prognosis and the potential role of maintenance antidepressant therapy in the elderly has not been investigated. Towards this end, our initial investigations have indicated that both major antidepressants, Nortriptyline (NT) and Phenelzine (PE) are significantly superior to placebo for successful treatment of geriatric depressions. In terms of safety, it has been shown that if judiciously used, both drugs are well tolerated in treating the acute phase of the depressive episode. Furthermore, preliminary results of our pilot longitudinal study provided evidence for the efficacy of antidepressant prophylaxis in geriatric depression. The objective of the present project is to validate and extend our preliminary findings. Specifically we will: 1) Further assess the validity of the preliminary findings on the comparative efficacy and safety of phenelzine (PE) and nortriptyline (NT), by extending our sample size (N=50) to another 80 (40 per group) carefully screened depressed elderly who will be randomly assigned to either NT or PE under double-blind conditions. We eliminate the placebo of the current study. 2) Investigate the comparative efficacy and safety of NT vs. PE vs. placebo for successful maintenance in acute phase responders to NT or PE. 3) Determine prognostic factors associated with optimal antidepressant efficacy and safety or preferential response to either drug during the acute phase, or optimal maintenance during the follow-up phase. To accomplish these aims, we intend to do the following: 1) Extend our original sample size (N=50) to another 80 (40 per group) carefully screened depressed elderly randomly assigned to NT or PE following a two week single blind placebo washout period. 2) Responders, following a period of stabilization (4 months), will be randomly assigned to NT or PE or to placebo for a period of two years. These further investigations will enable us to validate and extend our preliminary findings and provide important information regarding optimal pharmacological treatment and prophylaxis for this illness.